The class of compounds referred to as C-nucleosides has captured increased interest due to the effectiveness of many such compounds as antibiotics and potential anti-cancer compositions. The first member of this class to be discovered was pseudouridine, a naturally occurring nucleoside isolated from a variety of t-RNA's. The structure of pseudouridine has been identified as follows: ##STR2## It will be noted that this composition is a union of a heterocyclic moiety, uracil, and a carbohydrate moiety, ribofuranose, in the beta configuration.
Following the isolation of pseudouridine, two new C-nucleosides having strong antibiotic effects were discovered, formycin and formycin B, having the structural formulas illustrated below: ##STR3## Both compositions have shown additional activity in inhibiting leukemia L-1210, HeLa cells, Ehrlich carcinoma in mice and Yoshida rat sarcoma cells.
Following the isolation of several other C-nucleosides having various levels of antiviral and antitumor activity, a compound identified as oxazinomycin was extracted from the culture filtrate of Streptomyces tanesashiensis and from a Streptomyces strain sp. 80,432. Its structure is very similar to pseudouridine, as can be noted below. ##STR4## In addition to its anti-bacterial activity, this C-nucleoside exhibits a broad spectrum of antitumor activity, including Ehrlich mouse ascites carcinoma, sarcoma 180 (ascites) and sarcoma 180 (solid form) in vivo.
The antiviral and antitumor effects of the above mentioned compounds, and of the oxazinomycin in particular, suggest the utility of pseudouridine derivatives as potential candidates of similar activity. A primary difficulty in further analysis of pseudouridine was achieving blocked sites on the carbohydrate moiety to permit more detailed study of nucleophilic substitutions of the heterocyclic constituent. In addition, a blocked derivative of pseudouridine was required which could serve as an intermediate, from which various substituted compounds could be prepared.